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Could this be considered artificial life?


Reaper

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Recently there has been news that Craig Venter has made an artifical life form, but so far all of the articles come directly out of the mainstream media, and so far there really is no details about the experiment. Instead they dove right down to implications without explaining what they actually did. Also, I can't seem to find it anywhere in major scientific journals.

 

Here is one such article: http://www.guardian.co.uk/science/2007/oct/06/genetics.climatechange

 

Here they at least go over some of the details, and it doesn't seem like that they really created an artifical life form, rather they just took some existing chromosomes and modified it somewhat, which is something we've been able to do for a couple of decades now.

 

What is your take on this?

 

So far it seems to be an attempt at publicity

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The way I interpret is they copied the sequence of genes from another lifeform synthetically. If their copy is good, it should work as well as one made by nature. It does not create life any differently than inserting DNA from one lifeform into another. They sort of copied the Mona Lisa but didn't make an original work of art. Irregardless, this capability could come in handy, in the future.

 

The next step would be to understand the logic of DNA. One might want a green haired reptile with big eyes. Based on the logic of DNA, we would calculate the genes and their organization, and then use the above technique to fabricate these gene sequences, like an original work of art.

 

We know which genes do what, but the not all the logic of the ordering. If we took human DNA, and slice and diced it, and then put the puzzle of genes into another order, without losing any genes, it may not follow the logic to act the same way. It is sort of like building a bridge, one needs to set the footers and build the towers before the paving the road.

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Karona et al synthesized a complete gene chemically in 1970 (for which Karona won a Nobel Prize). It was a HUGE undertaking at the time mostly because of the adsence of automated DNA synthesizers. I don't see this as significant beyond that achievement except Venter and his cohorts have access to massively paralleled, high speed automated DNA synthesizers. Consequently, I consider this a simple matter of scale up. Of course that is my subjective opinion and there is a chance I could be underestimating the achievement, but at this point in time, that is how I see it.

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Ah, so we really can create our own DNA molecule from scratch. That's the easy part, I suppose. Next on the list is to start designing our own proteins. Various projects working on that, but it is insanely computationally expensive. Then we may need to figure out the non-coding DNA instructions, if those are vital.

 

I suppose this means that when we design a new protein, we can change the DNA of some bacterium so that it will produce it for us. Seems pretty useful...

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The way I interpret is they copied the sequence of genes from another lifeform synthetically. If their copy is good, it should work as well as one made by nature.

 

as i read it they punched out the unneccesary genes, so what they have is a bear minimum genome that's required for life. which is a bit more impressive... you could probably justify calling it a synthetic (sub?)species?

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In my opinion it does not qualify as artificial life at all. Essentially they mutated a chromosome to get rid of ~200 kb. Mutants are routinely constructed for a long while already (though I have to admit that my largest deletions were only around 20 kb). The major twist they did is to reinsert the mutated chromosome into the organism where it displaced the existing one (or rather they searched for those that did). However, I cannot see the fundamental differences than to mutate them in vivo (and prune the DNA down there), except for the working time. Other have curated larger sequences, though it was for extrachromosomal quasi essential genetic elements and not chromosomes.

To me it reads a bit more like Venter-ish publicity stunt (although in principle the results are not uninteresting).

The resulting organisms are termed mutant strains and are not considered an own species.

 

Also note that to my knowledge it is not possible to synthesize extremely large fragments completely de novo. It is possible to amplify existing chromosomes rather easily (with special polymerases) but de novo DNA synthesizers are limited to the synthesis of ~100 bp fragments.

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In my opinion it does not qualify as artificial life at all. Essentially they mutated a chromosome to get rid of ~200 kb. Mutants are routinely constructed for a long while already (though I have to admit that my largest deletions were only around 20 kb). The major twist they did is to reinsert the mutated chromosome into the organism where it displaced the existing one (or rather they searched for those that did). However, I cannot see the fundamental differences than to mutate them in vivo (and prune the DNA down there), except for the working time. Other have curated larger sequences, though it was for extrachromosomal quasi essential genetic elements and not chromosomes.

To me it reads a bit more like Venter-ish publicity stunt (although in principle the results are not uninteresting).

The resulting organisms are termed mutant strains and are not considered an own species.

 

Also note that to my knowledge it is not possible to synthesize extremely large fragments completely de novo. It is possible to amplify existing chromosomes rather easily (with special polymerases) but de novo DNA synthesizers are limited to the synthesis of ~100 bp fragments.

 

Can genes actually be reduced in computer terms, you speak of kb and bp which are usually applied to computer memory systems.

 

Anyways, I have yet to find it on any other scientific publications. It seems to me that this guy is probably trying to go for publicity so far. And in any case what he does has pretty much been done over and over again for several years now. I don't think it qualifies for artificial life.

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Can genes actually be reduced in computer terms, you speak of kb and bp which are usually applied to computer memory systems.

 

kb = kilo bases

bp = base pairs (in double stranded DNA)

 

Anyways, I have yet to find it on any other scientific publications. It seems to me that this guy is probably trying to go for publicity so far. And in any case what he does has pretty much been done over and over again for several years now. I don't think it qualifies for artificial life.

 

When was the last time that you heard an important scientific discovery announced in a news conference?

 

Also note that to my knowledge it is not possible to synthesize extremely large fragments completely de novo. It is possible to amplify existing chromosomes rather easily (with special polymerases) but de novo DNA synthesizers are limited to the synthesis of ~100 bp fragments.

 

Well, he could have just taken some existing chromosomes and/or plasmids then cleaved out what he didn't want with nucleases and ligated them together. If that is what did, wouldn't it be a big disappointment? Any claims about making it from "chemicals in the lab" would certainly be stretching it.

 

I suspect though that, with an automated DNA synthesizer, he synthesized fragments of a couple or a few hundred bases and then ligated these together. The "chemicals in the lab" would mostly consist of phophoramidites and enzymes; which are common in DNA synthesis and molec bio labs, but not what comes immediately to mind for most people. I think that would still be a disappointment because it is nothing but scale up of existing, done to death protocols.......on par with building the biggest brick wall in the world because you can afford more bricks than anyone else.

 

Plus, if the stories I've read are accurate, he pared down known genes, so he didn't design anything denovo.

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Any claims about making it from "chemicals in the lab" would certainly be stretching it.

One has to note that this part is not a quote but likely an interpretation of the author of the article. One has to await the actual publication, but ligating short synthesized fragments does appear like an utter waste of time to me.

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What they did was sort of put a new motor in an old car. They did build the motor from scratch, but used a motor building manual as their guide. The claim is this new motor makes a new type of artificial auto. They are sort of correct in the sense, this would not come off the assemble line of nature. The hope is they made their engine an upgrade compared to the production model. If they went from a big 8 down to a 4-cylinder, it may still work but may poke along. Maybe they can bore out the old 8 and add some genetic turbo, to try for a new high performance bacteria.

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Also note that to my knowledge it is not possible to synthesize extremely large fragments completely de novo. It is possible to amplify existing chromosomes rather easily (with special polymerases) but de novo DNA synthesizers are limited to the synthesis of ~100 bp fragments.

 

I have to revise my statement as I have stumbled across a paper describing the linkage of such short fragments utilising PCR and bridge oligos. But as long as they use the same backbone as the organism from which they put the chromosome back into it is imo still only a mutant (DNA is DNA and in vitro amplification of it is still old news).

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Here is a novel strategy for making more advanced life forms. This idea might be able to make use of the technology and techniques used in this discussion. If one tries to project into the future of the living state, images of things like triple helixes often appear. But this is not really energetically favorable since it would leave one of the strands of DNA without good H-bonds.

 

Another theoretical strategy, that keeps the DNA double helix, is to create a new base pair, so there are six bases and three pairs within the DNA double helix. What this does is radically increase the number of possible proteins that can be made with the mRNA. Even if three bases per amino acid is maintained, the number of possible amino acids opens wide. Life may not need that many, such that there may be a bump up, so four bases will be used for each amino acid. This still offering more choices, but with more reliability, causing the number of defects to decrease.

 

There are certain proteins that the cell uses other proteins to make. These proteins might be made more directly, so more energy can be used for other things. The cell may also generate a lot of junk that needs to be transported out the cell. This junk may be gold for another cell, allowing it to fill in the gaps between the junk it is generating, until useful appears. It is sort of sci-fi but within the realm of futuristic possibilities.

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  • 2 weeks later...
Ah, so we really can create our own DNA molecule from scratch. That's the easy part, I suppose. Next on the list is to start designing our own proteins.

 

That's been done. Including making the DNA and getting bacteria to express the gene and make the protein:

 

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17096543&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

 

Since I know, from experience, that you don't always read the information accurately, I'll put the Abstract for you and bold the relevant parts:

 

"Spider silk fibers have remarkable mechanical properties that suggest the component proteins could be useful biopolymers for fabricating biomaterial scaffolds for tissue formation. Two bioengineered protein variants from the consensus sequence of the major component of dragline silk from Nephila clavipes were cloned and expressed to include RGD cell-binding domains. The engineered silks were characterized by CD and FTIR and showed structural transitions from random coil to insoluble beta-sheet upon treatment with methanol. The recombinant proteins were processed into films and fibers and successfully used as biomaterial matrixes to culture human bone marrow stromal cells induced to differentiate into bone-like tissue upon addition of osteogenic stimulants. The recombinant spider silk and the recombinant spider silk with RGD encoded into the protein both supported enhanced the differentiation of human bone marrow derived mesenchymal stem cells (hMSCs) to osteogenic outcomes when compared to tissue culture plastic. The recombinant spider silk protein without the RGD displayed enhanced bone related outcomes, measured by calcium deposition, when compared to the same protein with RGD. Based on comparisons to our prior studies with silkworm silks and RGD modifications, the current results illustrate the potential to bioengineer spider silk proteins into new biomaterial matrixes, while also highlighting the importance of subtle differences in silk sources and modes of presentation of RGD to cells in terms of tissue-specific outcomes."

 

You might also be interested in the following paper:

J Thromb Haemost. 2005 Aug;3(8):1692-701.

 

The promise and challenges of bioengineered recombinant clotting factors.

 

Pipe SW.

 

Department of Pediatrics and Communicable Diseases, University of Michigan, Ann

Arbor, MI 48109, USA. ummdswp@med.umich.edu

 

The past 10 years of clinical experience have demonstrated the safety and

efficacy of recombinant clotting factors. With the adoption of prophylactic

strategies, there has been considerable progress in avoiding the complications of hemophilia. Now, insights from our understanding of clotting factor structure and function, mechanisms of hemophilia and inhibitors, gene therapy advances and a worldwide demand for clotting factor concentrates leave us on the brink of embracing targeted bioengineering strategies to further improve hemophilia therapeutics. The ability to bioengineer recombinant clotting factors with improved function holds promise to overcome some of the limitations in current treatment, the high costs of therapy and increase availability to a broader world hemophilia population. Most research has been directed at overcoming the inherent limitations of rFVIII expression and the inhibitor response. This includes techniques to improve rFVIII biosynthesis and secretion, functional activity,

half-life and antigenicity/immunogenicity. Some of these proteins have already

reached commercialization and have been utilized in gene therapy strategies,

while others are being evaluated in pre-clinical studies. These novel proteins

partnered with advances in gene transfer vector design and delivery may

ultimately achieve persistent expression of FVIII leading to an effective

long-term treatment strategy for hemophilia A. In addition, these novel FVIII

proteins could be partnered with new advances in alternative recombinant protein production in transgenic animals yielding an affordable, more abundant supply of rFVIII. Novel rFIX proteins are being considered for gene therapy strategies whereas novel rVIIa proteins are being evaluated to improve the potency and extend their plasma half-life. This review will summarize the status of current recombinant clotting factors and the development and challenges of recombinant clotting factors bioengineered for improved function."

 

The way I interpret is they copied the sequence of genes from another lifeform synthetically.

 

That doesn't appear to be what they did. Instead, they took nucleotides and a DNA synthesizer and, adding one base at a time, constructed a chromosome. From scratch. They based the sequence of bases on several existing chromosomes, but that would be like an engineer making a car but basing the design on earlier cars. The engineer still "made" the car if he machined all the parts himself and put them together.

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